Extended Data Fig. 10: Proposed model displaying the contribution of TET2 to the development and progression of PD.
From: Epigenomic analysis of Parkinson’s disease neurons identifies Tet2 loss as neuroprotective
TET2 is responsible for the conversion of DNA methylation to hydroxymethylation, and TET2 inactivation results in cytosine modification changes relevant to those observed in PD neurons. In PD, there is epigenetic dysregulation of the TET2 locus and an upregulation of TET2 expression, which leads to increased hydroxymethylation. Based on our study and the existing literature13,27,43, this could have two main consequences. First, elevated TET2 levels increases susceptibility to immune activation, promoting neuroinflammation. Second, TET2 upregulation activates genes involved in neurogenesis in post-mitotic neurons. Both of these aberrant processes may lead to the neurodegeneration observed in PD patients.
